This project considers certain features of aging cells in culture. The first portion deals with "Mixed Function Oxidation and Connective Tissue Modification" and "Prolyl Hydroxylase in Aging Fibroblast Cultures". The second portion examines the role of a vitamin K dependent bone protein, osteocalcin, in the etiology of senile osteoporosis. The third project examines the cell age dependence in the regulation of cholesterol biosynthesis. Evidence suggests that the number of LDL receptors decreases with the "age" of diploid fibroblast culture. The fourth project examines various X-linked parameters as indices of cell aging. In particular, it examines the X-linked HGPRT (hypoxanthine-guanine phosphoribosyl transferase system) and compares it ot the autosome linked APRT (adenine phosphoribosyl transferase) system as a function of cell age. Studies are also in progress on the synthesis of phosphoribosylpyrophosphate in aging cells. In general, this program examines a variety of cell and tissue "age" dependent properties which could be of considerable importance in geriatric medicine and in the understanding of maturity onset disorders.